ENDOTHELIAL MECHANOTRANSDUCTION MECHANISMS FOR VASCULAR PHYSIOLOGY AND ATHEROSCLEROSIS

Abstract

Vascular physiology and disease progression, such as atherosclerosis, are mediated by hemodynamic force generated from blood flow. The hemodynamic force exerts on vascular endothelial cells (ECs), which could perceive the mechanical signals and transmit them into cell interior by multiple potential shear sensors, collectively known as mechanotransduction. However, we do not understand completely how these shear-sensitive components orchestrate physiological and atherosclerotic responses to shear stress. In this review, we provide an overview of biomechanical mechanisms underlying vascular physiology and atherosclerotic progression. Additionally, we summarize current evidences to illustrate that atherosclerotic lesions preferentially develop in arterial regions experiencing disturbance in blood flow, during which endothelial dysfunction is the initial event of atherosclerosis, inflammation plays dominant roles in atherosclerotic progression, and angiogenesis emerges as compensatory explanation for atherosclerotic plaque rupture. Especially in the presence of systemic risk factors (e.g., hyperlipidaemia, hypertension and hyperglycemia), the synergy between these systemic risk factors with hemodynamic factors aggravates atherosclerosis by co-stimulating some of these biomechanical events. Given the hemodynamic environment of vasculature, understanding how the rapid shear-mediated signaling, particularly in combination with systemic risk factors, contribute to atherosclerotic progression through endothelial dysfunction, inflammation and angiogenesis helps to elucidate the role for atherogenic shear stress in specifically localizing atherosclerotic lesions in arterial regions with disturbed flow.